Chem3x11 Lecture 3

Key concepts

The preferred conformation of a substituted cyclohexane depends on what's attached to it

Two cyclohexanes can be fused to give decalins

Attachment of substituents to cyclohexanes can lock their conformations, giving complex, but very information-rich NMR spectra

Cyclohexanes with Two Substituents

cis and trans refer to Relative Stereochemistry. Nothing to do with Ring Flipping

We need to be clear on one thing from the outset. cis and trans isomers do not interconvert - they are separate structures that are configurational isomers (diastereomers). It's not like you can convert one to the other with a ring flip. Here are the cis and trans isomers of 1,2-dimethylcyclohexane.

Scheme 1:cis and trans Diastereomers of 1,2-Dimethylcyclohexane

Drawings like this allow us to see relative stereochemistry of those methyl groups, but we need to be happy thinking about the rings in 3D so we can think about what the preferred conformations might be. The easiest way to do this is to draw a cyclohexane ring, draw in one substituent, then draw in the other given the relative stereochemistry. Then perform a ring flip to get the other conformation. Here are the conformations for the cis isomer.

Scheme 2: Conformations of the cis Diastereomers of 1,2-Dimethylcyclohexane

In both cases one methyl is equatorial and one is axial. Both conformations are of the same energy. The trans isomer is different. In one conformation the methyls are both equatorial, and in the other they are both axial. Clearly these conformations will have different energies and the di-equatorial conformation is going to be favoured.

Scheme 3: Conformations of the trans Diastereomers of 1,2-Dimethylcyclohexane

Chirality of 1,2-Dimethylcyclohexane

Look at the two chair conformations of cis-1,2-dimethylcyclohexane. They're enantiomers. Does that mean this compound is chiral? No - the two conformations interconvert rapidly under normal conditions and we can't separate them. Incidentally they interconvert via a meso boat form.

Scheme 4:cis-1,2-Dimethylcyclohexane is "Achiral"

It's easier to see that the cis isomer is achiral with the 2D diagram, because there's an obvious plane of symmetry running through the molecule, but it's important also to be able to reach the same conclusion using a more grown-up 3D analysis of the molecule.

What about the trans isomer? Much more interesting. It's chiral, no matter what you do. Take the 2D drawing, draw the enantiomer. They're not the same. Further, when you draw the 3D conformation, and ring-flip, the ring-flipped conformations are not the same, nor are they enantiomers. This molecule is chiral, no matter what shape it adopts.

Decalins

Again, we can have cis and trans isomers that do not interconvert, no matter how much ring flipping etc you try to do.

Scheme 9:cis and trans Decalins Don't Interconvert

Drawing the preferred conformation of the trans fused system is straightforward. Both rings are chairs. The small Hs go axial, leaving the bulkier carbon chains to be equatorial.

Scheme 10: Drawing trans-Decalin

(but actually you can't do ring flipping in this compound - can you see why?)

Drawing the cis can give people nightmares, but stay calm and you'll be fine. Draw one ring. Take the two leftmost carbons and draw an axial C-C bond down and an equatorial C-C bond. That starts you on the second ring, which then also needs to come out chair-like, and it's often easier to draw that in if you rotate your page (or your mind, or both) to see that second ring as a chair.

Scheme 11: Drawing cis-Decalin

Why do we care about decalins? One of the most important classes of natural molecules, the steroids, have these structures in them. They are synthesised by an extraordinarily cool reaction, and the resulting shape of the molecule is partly determined by the fact that these trans ring junctions are a little more stable than the cis, all other things being equal. Look at the following structures to see if you are happy that the 2D drawings imply the 3D structures and vice versa.

Scheme 12: Decalins Occur in Steroids

The Licence for This Page

Is CC-BY-3.0 meaning you can use whatever you want, provided you cite me.